摘要
目的:研究厚朴酚对肠道致病菌的体外抑菌作用和机理,以及其与诺氟沙星的协同抗菌作用,为治疗细菌性肠道传染病的新药开发提供参考。方法:采用微量肉汤二倍稀释法测定厚朴酚、诺氟沙星对大肠埃希菌、福氏志贺菌、宋内志贺菌、肠炎沙门菌、副溶血弧菌的最低抑菌浓度(minimum inhibitory concentration,MIC);采用棋盘法测定厚朴酚和诺氟沙星联用的抑菌浓度指数(fractional inhibitory concentration index,FICI);采用生物化学法测定厚朴酚对致病菌胞外核酸、蛋白质含量的影响,采用荧光分光光度法测定膜电位强度,分析厚朴酚对肠道致病菌的抑菌机理。结果:厚朴酚对大肠埃希菌、福氏志贺菌、宋内志贺菌、肠炎沙门菌、副溶血弧菌的MIC为256~4096μg/mL,对福氏志贺菌的抑菌活性最强;与诺氟沙星联用的FICI为0.375~1,表现为协同或相加作用;福氏志贺菌经MIC的厚朴酚作用6 h后,细胞外的核酸水平、蛋白质含量均显著升高(P<0.01),细胞内的荧光强度显著降低(P<0.01),表明福氏志贺菌细胞膜受到一定程度的损伤甚至破裂。结论:厚朴酚对肠道致病菌具有优良的抗菌作用,作用机理与破坏细胞膜完整性有关;同时,厚朴酚与诺氟沙星联用可发挥协同或相加的抗菌作用,可为临床细菌性肠道传染病的治疗提供新策略。
Objective:To investigate the in vitro antibacterial activity and mechanism of magnolol against enteric pathogenic bacteria,as well as its synergistic antibacterial effect with norfloxacin,and provide a reference for the development of new drugs for the treatment of bacterial intestinal infectious diseases.Methods:The microbroth double dilution method was used to determine the minimum inhibitory concentration(MIC)of magnolol and norfloxacin against Escherichia coli,Shigella flexneri,Shigella sonnei,Salmonella enteritidis and Vibrio parahaemolyticus.The checkerboard method was used to measure the fractional inhibitory concentration index(FICI)of the combination of magnolol and norfloxacin.Biochemical methods were used to determine the effects of magnolol on the extracellular nucleic acid and protein contents of pathogenic bacteria,and fluorescence spectrophotometry was employed to determine the membrane potential intensity,so as to analyze the antibacterial mechanism of magnolol against enteric pathogenic bacteria.Results:The MIC values of magnolol against Escherichia coli,Shigella flexneri,Shigella sonnei,Salmonella enteritidis and Vibrio parahaemolyticus ranged from 256 to 4096μg/mL,with the strongest antibacterial activity against Shigella flexneri.The FICI values of magnolol combined with norfloxacin were 0.375-1,indicating a synergistic or additive effect.After Shigella flexneri was treated with magnolol at the MIC for 6 hours,the extracellular nucleic acid level and protein content increased significantly(P<0.01),while the intracellular fluorescence intensity decreased significantly(P<0.01),suggesting that the cell membrane of Shigella flexneri was damaged or even ruptured to a certain extent.Conclusion:Magnolol has excellent antibacterial activity against enteric pathogenic bacteria,and its mechanism of action is related to the destruction of cell membrane integrity.Meanwhile,the combination of magnolol and norfloxacin can exert synergistic or additive antibacterial effects,which can provide a new strategy for the clinical treatment of bacterial intestinal infectious diseases.
作者
邹茜
张鹏
陈秋铃
林思琦
陈彭龙
ZOU Qian;ZHANG Peng;CHEN Qiu-ling;LIN Si-qi;CHEN Peng-long(The First Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510422,China;Affiliated Hospital of Jiujiang University,Jiujiang Jiangxi 332000,China)
出处
《抗感染药学》
2025年第7期641-645,共5页
Anti-infection Pharmacy
基金
广东省中医药局科研项目(编号:20241106)。
关键词
厚朴酚
肠道致病菌
抗菌作用
作用机理
联合抗菌
magnolol
enteric pathogenic bacteria
antibacterial activity
mechanism of action
combined antibacterial therapy
